According to the researchers, these cells are more susceptible to HIV infection, support the highest levels of infection, and are the more likely to transfer HIV to CD4 T cells following infection.
Australian researchers from The Westmead Institute for Medical Research have identified new immune cells at the frontline of HIV infection: CD11c+ dendritic cells. According to the researchers, these cells are more susceptible to HIV infection, support the highest levels of infection, and are the more likely to transfer HIV to CD4 T cells following infection.
These cells are a subset of dendritic cells only found in human genital tissues at the epithelial level of the vagina, inner foreskin, and anus. Due to its location in genital tissue, the cells are the first immune cells to interact with the HIV virus upon infection. The role of these cells is to capture incoming disease-causing viruses or bacteria and deliver them to CD4 T cells and prepare the immune system to either tolerate or attack the virus or bacteria.
“Interestingly, they are also the primary HIV target cells in which the virus replicates,” said Andrew Harman, PhD, BSc, associate professor of Applied Medical Sciences at The University of Sydney, Applied Medical Sciences Honors Coordinator at The Westmead Institute for Medical Research, and co-lead author of the study, who explained in a statement that if CD4 T cells fall below critical levels, as seen in HIV patients, the body is no longer able to illicit an immune response.
During the study, the researchers obtained human abdominal and genital tissues within 30 minutes of surgery from 75 patients undergoing plastic surgery, circumcision, gender reassignment, or colorectal surgery.
Traditionally, langerhans cells (LCs) have been thought to be the only mononuclear phagocyte population in the epidermis, where they detect pathogens. However, by analyzing these tissues, the researchers were able to show that CD11c+ cells are also present. While CD11c+ cells were less abundant than LCs, they were present in easily identifiable proportions in almost every doner. Compared to LCs, they are enriched in anogenital tissues where they preferentially interact with HIV.
“We were able to look at the tissue only 20 minutes after it had been surgically removed from the body and also developed group breaking RNAscope technology which allowed us to watch as living CD11+c dendritic cells took up the virus and delivered it to the CD4 T cells,” said Harman.
These findings were observed using both a lab-adapted and transmitted strain of HIV.
The study has 2 important implications for HIV research, said Tony Cunningham, professor of Research Medicine at The University of Sydney Medical School, executive director of The Westmead Institute for Medical Research, and co-lead author of the study, in a statement. First, the findings open the door to potentially developing strategies to block the transmission of HIV by blocking the virus’ ability to bind to the CD11+c dendritic cells and thus prevent their ability to transmit the virus to CD4 T cells.
There is also potential for an HIV vaccine, which has represented a significant challenge for researchers for years. If HIV fragments or inactivated HIV were able to be targeted at these CD11+c dendritic cells, it could have the potential to prime an immune response against HIV once it enters the body.
Bertram K, Botting R, Baharlou H, et al. Identification of HIV transmitting CD11c+ human epidermal dendritic cells [published online June 21, 2019]. Nat Commun. doi: 10.1038/s41467-019-10697-w.